RLS (Didriksen, 2020) – Is Restless Leg Syndrome Genetic?

Nebula Genomics DNA Report for Restless Leg Syndrome

Is restless leg syndrome genetic? We created a DNA report based on a study that attempted to answer this question. Below you can see a SAMPLE DNA report. To get your personalized DNA report, purchase our Whole Genome Sequencing!

restless leg syndrome sample report from Nebula Genomics
restless leg syndrome sample variants from Nebula Genomics
To learn more about how Nebula Genomics reports genetic variants in the table above, check out the Nebula Research Library Tutorial.

What is Restless Leg Syndrome?

Restless leg syndrome (RLS), also called Willis-Ekbom Disease, is a long term neurological condition associated with the constant need to move one’s legs. At times, it affects the arms as well as the legs. Patients describe symptoms as aching, tingling, or crawling. As these experiences are most common at rest, including while trying to sleep, the CDC classifies the condition as a sleep disorder. Notably, this factor can cause daytime sleepiness and insomnia. Limb twitching during sleep, known as periodic limb movement disorder, is also common. 

Moving the legs will temporarily relieve the discomfort.

Restless leg syndrome causes mild to severe discomfort
Restless leg syndrome causes mild to severe discomfort. Wikipedia. CC0 1.0 Universal Public Domain Dedication.

There are two types, mainly based on the onset of the condition. If it occurs before the middle age of 45, it is known as early onset RLS. This form runs in families and can worsen over time. When it occurs after the age of 45, it is known as late onset RLS. The latter form comes on suddenly and does not worsen.

Doctors diagnose restless leg syndrome by observing symptoms and ruling out other causes. It can be associated with other conditions and medications. Sometimes, the condition resolves on its own. If there is an underlying problem, treatment of the cause will alleviate the RLS as well. Lifestyle changes and certain medications can also help with the condition.

Is Restless Leg Syndrome Genetic?

Restless leg syndrome is most likely a combination of genetic and environmental factors. Several genes have been associated with developing the conditions. Most are thought to be involved in the development of nerve cells (neurons) before birth. Although not identified, genes associated with iron levels or dopamine signaling may also play a role. 

Early onset RLS is more likely than the late onset form of the disease to be caused by genetics. 

Epidemiology (Part 3 of Is restless leg syndrome genetic?)

The prevalence of restless leg syndrome varies widely based on geographical location. There has historically been difficulty in obtaining accurate numbers due to the fact that many symptomatic patients do not seek treatment. Thus, studies must be carried out through one-on-one interviews or surveys. 

In 2006, RLS was shown to be a common disorder with prevalence rates ranging between 2.5 and 10% of the population. North American and European populations accounted for higher rates while Asian population values were lower. For example, a 2000 study in the United States found a prevalence as high as 20% in adults.

In 2017, a collection of studies suggested that the prevalence rose to 3.9-15% of the general population. This includes 7-10% in Caucasians and 0.1 to 12% among Asian population. Higher rates appear in Western countries. In the United States, the current rate is estimated at 7-10%.

Although it can occur at any point in life, risk and severity of the condition increases with age. Additionally, incidence is twice as high in women as men. 

Symptoms (Part 4 of Is restless leg syndrome genetic?)

Symptoms of restless leg syndrome usually focus on physical sensations of the legs and behavioral changes. Leg discomfort is described as creeping, itching, pulling, crawling, tugging, throbbing, burning, or gnawing. Sitting, lying down, and overall little leg movement exacerbates these symptoms. Because of this discomfort, patients describe an uncontrollable need to move their legs. The effects of RLS include:

  • Sleep disruption, including difficulty falling asleep and staying asleep
  • Daytime sleepiness
  • Struggles with behavior and work performance (irritability, moodiness, difficulty concentrating, hyperactivity, etc.)
Changes in sleep patterns
Restless leg syndrome is known for disrupting sleep. Wikipedia. CC-Attribution-Share Alike 3.0 Unported.

Symptoms can be mild or severe. On the mild end, a person may experience symptoms only a few times a month. For others, they may be as persistent as every night. In the most severe cases, the symptoms can affect the arms or other parts of the body. 

Causes (Part 5 of Is restless leg syndrome genetic?)

In most cases, the cause of restless leg syndrome is unknown. In most cases diagnosed before the age of 40, there appears to be a hereditary component. 

Overall, the symptoms are associated with the basal ganglia, the part of the brain that controls movement. Low iron levels may be the main cause through disruption of the chemical dopamine, which can result in involuntary movement, such as that seen with this condition. Other movement disorders, such as diabetes, multiple sclerosis, rheumatoid arthritis, and Parkinson’s disease, also increase the risk of developing restless leg syndrome.

Restless leg syndrome as a result of fibromyalgia
Restless leg syndrome is often caused by other diseases. Wikipedia. CC0 1.0 Universal Public Domain Dedication.

The National Institute of Neurological Disorders and Strokes lists the other conditions and medications that may contribute to developing the restless leg syndrome symptoms:

  • Kidney failure and hemodialysis
  • Iron deficiency (anemia)
  • Use of alcohol, nicotine, and caffeine
  • Pregnancy, especially in the last trimester
  • Neuropathy (nerve damage)
  • Anti nausea drugs
  • Antipsychotic drugs
  • Antidepressants that increase serotonin
  • Some cold and allergy medications that contain older antihistamines (e.g., diphenhydramine)

Diagnosis (Part 6 of Is restless leg syndrome genetic?)

The diagnosis of restless leg syndrome is based on a patient’s medical history and expression of symptoms. The International Restless Legs Syndrome Study Group has a list of criteria for positive diagnosis:

  • A strong, often irresistible urge to move your legs, usually accompanied by uncomfortable sensations.
  • Symptoms start or get worse when you’re resting, such as sitting or lying down.
  • Symptoms are partially or temporarily relieved by activity, such as walking or stretching.
  • Symptoms are worse at night.
  • Symptoms can’t be explained solely by another medical or behavioral condition.

If your doctor suspects that the symptoms are being caused by an underlying medical condition, they may order a physical or neurological exam or blood tests for conditions such as anemia. 

Depending on how severely the condition is affecting your sleep, the doctor may recommend you see a sleep specialist. This specialist can also use sleep studies to test for conditions such as sleep apnea. 

Treatment (Part 7 of Is restless leg syndrome genetic?)

If the RLS is caused by an underlying condition, treatment of that ailment will normally improve the symptoms. For example, if iron deficiency is detected, iron supplementation via oral or intravenous means may be recommended.

When no underlying condition is detected, lifestyle changes and medications may be prescribed to improve sleep and quality of life. Mayo Clinic describes some of these approaches.

Lifestyle changes

Simple lifestyle changes can help alleviate the symptoms although they do not address the underlying cause of RLS itself.

  • Warm baths and leg messages can help relax nervous muscles
  • Warm and/or cold packs help relax muscle sensations
  • Good sleep hygiene that includes a cool, quiet, comfortable sleeping environment; a consistent sleep schedule; and at least seven hours of sleep nightly
  • Moderate, regular exercise
  • Avoiding caffeine
  • A foot wrap specifically for RLS that creates certain pressure points


Prescription medications may be recommended if the symptoms persist or are severe. 

Medications that increase dopamine in the brain: These medications alter the levels of dopamine in the brain, which may biologically cause the symptoms. Several options are approved by the Food and Drug Administration (FDA) for RLS. Mild side effects include nausea, lightheadedness, and fatigue. Some people with RLS may also experience impulse control issues due to the change in brain chemistry associated with this medication. 

Medications that affect calcium channels: These medications can also alter brain chemistry which affects symptoms.   

Opioids: These narcotics are often effective to treat RLS symptoms ranging from mild to severe. They should be prescribed carefully as they can be addicting. 

Muscle relaxants and sleep medications: These medications are used to help patients sleep better at night. They do not relieve the symptoms of RLS and can cause daytime drowsiness. Therefore, they are usually only recommended after other treatment options have failed. 

Some medications, including some antidepressants, some antipsychotic medications, some anti-nausea drugs, and some cold and allergy medications, may make symptoms worse. 

Did you like this article? Be sure to check out the other posts in the Nebula Research Library!

January 5, 2022